Introduction

The PTPN22 gene is an important risk factor for human autoimmunity. Two PTPN22 missense-SNPs, both with functional influence, the R620W (1858C>T, rs2476601) in
exon 14 and the R263Q (788G>A, rs33996649) in exon 10 have been associated with autoimmune
diseases [1-4].

Aim

The aim of this study was to evaluate for the first time the role of the R263Q PTPN22 polymorphism in ulcerative colitis (UC) and Crohn’s disease (CD), and re-evaluated
the association of the R620W PTPN22 polymorphism with both diseases.

Patients and methods

A total of 1,677 UC patients, 1,903 CD patients and 3,107 healthy controls, from an
initial case-control set of Spanish Caucasian ancestry and two independent sample
sets of European ancestry (Dutch and New Zealand), were included in the study. Genotyping
was performed using TaqMan SNP assays for the R263Q and R620W PTPN22 polymorphisms. Meta-analysis was performed on 6977 CD, 5695 UC and 9254 controls
to test the overall effect of the minor allele of R620W variant, and on the three
Caucasian cohorts for the R263Q polymorphism.

Results

The PTPN22 263Q loss-of-function variant showed an initial evidence of a significant association
with UC in the Spanish cohort (p=0.026,OR=0.61,95%CI=0.39-0.95), which was confirmed
in the meta-analysis (p=0.013pooled,OR=0.69,95%CI=0.51-0.93). In contrast, the 263Q
allele showed no association to CD, (p=0.22pooled,OR=1.16,95%CI=0.91-1.47). We found
in the pooled analysis that the PTPN22 620W gain-of-function variant was associated
with reduced risk of CD (p=7.4E-06pooled, OR=0.81,95%CI=0.75-0.89) but not of UC (p=0.88pooled,
OR=0.98,95%CI=0.85-1.15).

Conclusion

Our data suggest that two autoimmunity-associated polymorphisms of the PTPN22 gene are differentially associated with CD and UC. The R263Q polymorphism only associated
with UC meanwhile the R620W was significantly related with CD. Our findings support
the idea that the two major IBD phenotypes differ in some genetic components, and
also in specific variants within a single gene, thus suggesting the involvement of
different immunological mechanisms with a related nature.